Determinação da glico-hemoglobina : relação com a glicemia e aspectos analíticos

A glico-hemoglobina (HbA1c) é um parâmetro importante no controle glicêmico de pacientes diabéticos. Vários estudos clínicos mostraram claramente que a melhora no controle glicêmico está fortemente associada com a diminuição no desenvolvimento e/ou progressão das complicações microvasculares do diabetes. A medida exata e precisa da HbA1c é uma questão importante para os laboratórios clínicos. Vários fatores afetam os resultados e podem levar a resultados errôneos. Este trabalho analisou o efeito de fatores analíticos, estados patológicos e drogas nos resultados de HbA1c. Em um primeiro estudo, demonstramos que a fração lábil de HbA1c contribui significativamente para o resultado final. Quando está fração é separada inadequadamente, há a necessidade de um pré - tratamento na amostra, para evitarmos valores falsamente elevados. O armazenamento das amostras é um fator pré – analítico importante. Amostras mantidas sob refrigeração são estáveis por 10 dias e o armazenamento a longo prazo deve ser feito a – 80oC. No entanto, amostras congeladas a –20oC apresentam uma diminuição significativa nos valores de HbA1c, já nas primeiras 24h de armazenamento. Em um segundo estudo, relatamos que as hemoglobinas anômalas estão associadas com valores muito baixos de HbA1c. Adicionalmente, também demonstramos que a anemia é uma importante fonte de interferência negativa nos resultados. Sugerimos que, para a correta interpretação dos valores de HbA1c, o estado hematológico do paciente seja sempre considerado. Em um terceiro estudo, analisamos o uso crônico de aspirina, vitamina C e vitamina E nos níveis de HbA1c. Houve inexistência de efeito significativo nos resultados de HbA1c, medidos por 3 métodos rotineiramente utilizados pelos laboratórios clínicos, em indivíduos não - diabéticos. O clínico deve conhecer os fatores que afetam a determinação de HbA1c na população atendida e os resultados discordantes com a história clínica do paciente devem ser sempre investigado.

Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1

Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DM

Avaliação da presença de osteopatia decorremte do diabetes tipo 1 em criança e adolecentes do Rio Grande do Norte

Diabetes Mellitus (DM) and osteoposes are chronic diseases with great socioeconomic consequences, mainly due to the late complications and consequent disabilities. The potential effects of DM on bone metabolism remain a very conroversial issue, and disagreement exists with regard to the clinical implications of diabetic osteopenia and the mechanism of its ocurrence. The issue is further complicated by the contribuicion of the especific factors, such as duration of disease an dthe degree of metabolic control. The objective of this study is to identify the osteopathy in children and adolescents with DM 1 assisted in the hospital of pediatrics, UFRN, through biochemical markers of bone and mineral metabolism and the extent of bone mineral density. The study was composed by 74 diabetics type 1 patients (DM1) of both gender and aged 6 to 20 yars. Normoglicêmic group was composed by 97 healthy subjects of both genders, which showed the same age range of DM1, in addition to same socioeconomic class. These individuals qere students from the networks of public education in the city of Natal-RN, randomly invited to paticipate in our study. Both groups DM1 and NG were divided intofour subgroups, according to the classification of tanner , T1, T2, T3, T4 for achieving a benchmark. Diabetic individuals showed up with a poor glycemic control. the group DN1 T4 showed an incresead value for total protein, albumin, urea and microalbumiuria are predictors of grumelura injury in DM1 patients . The total alkaline phosphatase activitywas kept on high levels for both groups because they are in a stature development age. For osteocalcin there were decreased levels for groups Dm1 T1, T2, and T3 when compared to their NG (s), suggesting that this decrease could be associated with reduction in the number and/or differentiation os osteoblasts thereby contributing to reducing bone formation. There were no changes in the activity of TRAP. The serum concentrations of total and ionized calcium, phosphorus and magnesium were included within the RV. It was observed that the BMD (Z- SCORE ) has always been within the RV for both groups, despite to DM1 T4. Taking all together, our results support the hypothesis that children and adolescents with type 1 DM present the risk in the long run to suffer a reduction in the bone mass, associated to poor glicemic control and disease duration. It could limit the bone growth and increase the probality of development of osteopenia, as well as other complications surch as retinopathy and renal failure

Avaliação do status antioxidante, expressão gênica e polimorfismos dos genes SOD1, SOD2 e GPx1 em crianças, adolescentes e adultos jovens com diabetes tipo 1

Studies report that the pathophysiological mechanism of diabetes complications is associated with increased production of Reactive Oxygen Species (ROS)-induced by hyperglycemia and changes in the capacity the antioxidant defense system. In this sense, the aim of this study was to evaluate changes in the capacity of antioxidant defense system, by evaluating antioxidant status, gene expression and polymorphisms in the genes of GPx1, SOD1 and SOD2 in children, adolescents and young adults with type 1 diabetes. We studied 101 individuals with type 1 diabetes (T1D) and 106 normoglycemic individuals (NG) aged between 6 and 20 years. Individuals with type 1 diabetes were evaluated as a whole group and subdivided according to glycemic control in DM1G good glycemic control and DM1P poor glycemic control. Glycemic and metabolic control was evaluate by serum glucose, glycated hemoglobin, triglycerides, total cholesterol and fractions (HDL and LDL). Renal function was assessed by measurement of serum urea and creatinine and albumin-to-creatinine ratio (ACR) in spot urine. Antioxidant status was evaluate by content of reduced glutathione (GSH) in whole blood and the activity of erythrocyte enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). We also analyzed gene expression and gene polymorphisms of GPx1 (rs1050450), SOD1 (rs17881135) and SOD2 (rs4880) by the technique of real-time PCR (Taqman®). Most individuals with DM1 (70.3%) had poor glycemic control (glycated hemoglobin> 8%). Regarding the lipid profile, individuals with type 1 diabetes had significantly elevated total cholesterol (p <0.001) and LDL (p <0.000) compared to NG; for triglycerides only DM1NC group showed significant increase compared to NG. There was an increase in serum urea and RAC of individuals with DM1 compared to NG. Nine individuals with type 1 diabetes showed microalbuminuria (ACR> 30 mg / mg). There was a decrease in GSH content (p = 0.006) and increased erythrocyte GPx activity (p <0.001) and SOD (p <0.001) in DM1 group compared to NG. There was no significant difference in the expression of GPx1 (p = 0.305), SOD1 (.365) and SOD2 (0.385) between NG and DM1. The allele and genotype frequencies of the polymorphisms studied showed no statistically significant difference between the groups DM1 and NG. However, the GPx1 polymorphism showed the influence of erythrocyte enzyme activity. There was a decrease in GPx activity in individuals with type 1 diabetes who had a polymorphic variant T (p = 0.012). DM1 patients with the polymorphic variant G (AG + GG) for polymorphism of SOD2 (rs4880) showed an increase in the RAC (p <0.05). The combined data suggest that glucose control seems to be the predominant factor for the emergence of changes in lipid profile, renal function and antioxidant system, but the presence of the polymorphisms studied may partly contribute to the onset of complications

Transient bilateral diabetic cataracts in a Brazilian Terrier puppy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats

Purpose: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. Methods: 60 adult rats were randomly distributed into (n= 10/group): non-diabetic exposed to filtered air (G1); non-diabetic exposed to cigarette smoke only before pregnancy (G2); non-diabetic exposed to cigarette smoke before and during pregnancy (G3); diabetic exposed to filtered air (G4); diabetic exposed to cigarette smoke only before pregnancy (G5), and diabetic exposed to cigarette smoke before and during pregnancy (G6). Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. Results: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43 +/- 0.43), G3 (3.20 +/- 0.49), G4 (2.62 +/- 0.34), G5 (2.65 +/- 0.27) and G6 groups (1.94 +/- 0.35) presented decreased liver glycogen concentrations compared to G1 (4.20 +/- 0.18 mg/100mg liver tissue) (p<0.05). G5 and G6 groups presented decreased maternal weight gain and litter weight. Conclusions: Severe diabetes and cigarette smoke exposure, alone or associated, caused impairment in liver glycogen storage at term pregnancy. Due to the fact that liver glycogen storages were considered determinant for glucose tolerance, it is relevant to point out a rigid clinical glycemic control and to stop smoking so earlier in pregnancy programming.

Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions

Bauhinia forficata, commonly known as paw-of-cow, is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4(th) day of pregnancy, 600 mg/kg from 5(th) to 14(th) day and 1000 mg/kg from 15(th) to 20(th) day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, bypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation.

Fatores de risco para macrossomia fetal em gestações complicadas por diabete ou por hiperglicemia diária

OBJETIVO: identificar fatores de risco para a macrossomia fetal na população de gestantes portadoras de diabete ou hiperglicemia diária. MÉTODOS: estudo retrospectivo, tipo caso-controle, incluindo 803 pares de mães e recém-nascidos desta população específica, distribuídos em dois grupos: macrossômicos (casos, n=242) e não macrossômicos (controles, n=561). Foram comparadas variáveis relativas à idade, paridade, peso e índice de massa corporal (IMC), ganho de peso (GP), antecedentes de diabete, hipertensão arterial e tabagismo, tipo e classificação do diabete e indicadores do controle glicêmico no terceiro trimestre. As médias foram avaliadas pelo teste F e as variáveis categorizadas foram submetidas à análise univariada, utilizando-se o teste do chi². Os resultados significativos foram incluídos no modelo de regressão múltipla, para identificação do risco independente de macrossomia, considerando-se OR, IC 95% e valor de p. Para todas as análises foi estabelecido o limite de significância estatística de 5% (p<0,05). RESULTADOS: observou-se associação significativa entre macrossomia e GP maior que 16 kg, IMC >25 kg/m², antecedentes pessoais, obstétricos e, especificamente, o de macrossomia, classificação nos grupos de Rudge (IB e IIA + IIB), média glicêmica (MG) >120 mg/dL e média de glicemia pós-prandial >130 mg/dL no terceiro trimestre. Na análise de regressão múltipla, o GP >16 kg (OR=1,79; IC 95%: 1,23-1,60), o IMC >25 kg/m² (OR=1,83; IC 95%: 1,27-2,64), o antecedente pessoal de diabete (OR=1,56; IC 95%: 1,05-2,31) e de macrossomia (OR=2,37; IC 95%: 1,60-3,50) e a MG >120 mg/dL no terceiro trimestre (OR=1,78; IC 95%: 1,13-2,80) confirmaram risco independente para macrossomia nestas gestações de risco. CONCLUSÃO: o GP superior a 16 kg, o IMC maior ou igual a 25 kg/m², a MG superior a 120 mg/dL no terceiro trimestre e a presença de antecedentes pessoais de diabete ou de macrossomia foram identificados como fatores de risco para macrossomia fetal em gestantes portadoras de diabete ou de hiperglicemia diária.

The influence of short-term diabetes mellitus and insulin therapy on alveolar bone loss in rats

Background: It is well known that the multiple direct and indirect consequences of hyperglycemia in diabetic individuals have been linked to a number of abnormal host effector mechanisms that could lead to an increased risk of developing periodontal disease.Objective: the aim of this study was to investigate the effect of short-term experimental diabetes and insulin therapy on the severity of alveolar bone loss in rats, and the effect of experimental periodontitis on glycemic control.Methods: Seventy-two male Wistar rats were divided into four groups: group I animals were submitted to dental ligature around lower right first molars (ligated); group II consisted of streptozotocin (STZ)-diabetic, ligated rats; group III represented STZ-diabetic, unligated rats; and group IV consisted of insulin-treated (6 U/day), STZ-diabetic, ligated rats. Blood glucose of all diabetic rats was monitored at regular intervals. Standardized digital radiographs were taken after killing at 7, 15 and 30 days to measure the amount of bone loss about the mesial root surface of the first molar tooth in each rat.Results: No significant (p < 0.05) changes in plasma glucose levels of insulin-treated diabetic rats were found among the different examinations after the beginning of insulin therapy. Rats from group II showed significantly greater increases in mean plasma glucose levels at 15 and 30 days after ligature placement compared with rats from group III (p < 0.05). Furthermore, in spite of the significant alveolar bone loss progression that was observed in groups I, II and IV (p < 0.00001; two-way ANOVA), no significant differences among these groups regarding the severity of bone loss (p = 0.77) and no significant interaction between treatment group and time (p = 0.81) were found.Conclusions: Within the limits of this study, it can be suggested that the severity of periodontal disease was not affected by short-term diabetes, and that experimental periodontitis increased blood glucose levels in uncontrolled diabetic rats.

The Short-Term Effectiveness of Non-Surgical Treatment in Reducing Levels of Interleukin-1 beta and Proteases in Gingival Crevicular Fluid From Patients With Type 2 Diabetes Mellitus and Chronic Periodontitis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ultrastructural and proliferative features of the ventral lobe of the prostate in non-obese diabetic mice (NOD) following androgen and estrogen replacement associated to insulin therapy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Focus on Vitamin D, Inflammation and Type 2 Diabetes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hypertensive disorders in pregnant women with diabetes mellitus

The present study was performed to assess the rate of hypertensive complications in diabetic pregnant patients and the influence of White's classification and the quality of the diabetic control. This study included 169 diabetic pregnant women who had delivered at the University Hospital of Botucatu Brazil from 1980 to 1981. The hypertensive disorders occurred in 29.8% of the cases. The incidence of the hypertensive process was the same in all classes of diabetic patients, and it was independent of the glycemic control. In patients with gestational diabetes (classes A and AB), chronic hypertension was the commnest type found; in patients with short-term diabetes (classes B and C) pregnancy-induced hypertension (PIH) and chronic hypertension with superimposed PIH was the most frequent type, and diabetic patients with vasculopathies (classes D-R) had preeclampsia and chronic hypertension with superimposed preeclampsia as the commonest type found.

Acute and short-term insulin-induced molecular adaptations of GLUT2 gene expression in the renal cortex of diabetic rats

Increased GLUT2 gene expression in the renal proximal tubule of diabetic rats is an adaptive condition, which may be important in the diabetic nephropathy development. We investigated the effects of insulin treatment upon the renal GLUT2 overexpression of diabetic rats. Acute treatment, surprisingly, induced a rapid further increase in GLUT2 mRNA content. Twelve hours after insulin injection, GLUT2 mRNA was twice the value of saline-injected rats (P < 0.001), when GLUT2 protein remained unchanged. In response to short-term treatment, both GLUT2 mRNA and protein were increased in 1-day treated rats (P < 0.05 versus saline-injected), decreasing after that, and reaching, within 6 days, values close to those of non-diabetic rats. Concluding, insulin treatment induced: initially, an additional upregulation of GLUT2 gene expression, involving posttranscriptional modulation; thereafter, downregulation of GLUT2 expression, which returns to non-diabetic levels. The former may be related to increased insulin concentration, the latter may be due to glycemic control. © 2005 Elsevier B.V. All rights reserved.

Insulinoterapia, controle glicêmico materno e prognóstico perinatal - Diferença entre o diabetes gestacional e o clínico

PURPOSE: to evaluate the insulin therapy protocol and its maternal and perinatal outcome in patients with clinical or gestational diabetes in a high risk reference service. METHODS: descriptive and prospective study including 103 pregnant women with gestational or clinical diabetes treated with insulin and attended by the reference service from October 2003 to December 2005. Gemellarity, miscarriages, unfinished prenatal care and deliveries not attended by the service were excluded. The gestational age at the beginning of the treatment, dosage, doses/day, increment of insulin (UI/kg), glycemic index (GI) and perinatal outcomes were compared. ANOVA, Fisher's exact test and Goodman's test considering p<0.05 were used. RESULTS: multiparity (92 versus 67.9%), pre-gestational body mass index (BMI) >25 kg/m 2 (88 versus 58.5%), weight gain (WG) <8 kg (36 versus 17%) and a high increment of insulin characterized the gestational diabetes. For the patients with clinical diabetes, despite the highest GI (120 mg/dL (39.2 versus 24%)) at the end of the gestational period, insulin therapy started earlier (47.2 versus 4%), lasted longer (56.6 versus 6%) and higher doses of insulin (92 versus 43 UI/day) were administered up to three times a day (54.7 versus 16%). Macrosomia was higher among newborns from the cohort of patients with gestational diabetes (16 versus 3.8%), being the only significant neonatal outcome. There were no neonatal deaths, except for one fetal death in the cohort of patients with clinical diabetes. There were no differences in the other neonatal complications in both cohorts, and most of the newborns were discharged from hospital up to seven days after delivery (46% versus 55.8%). CONCLUSIONS: the analysis of these two cohorts has shown differences in the insulin therapy protocol in quantity (UI/day), dosage (UI/kg weight) and number of doses/day, higher for the clinical diabetes cohort, and in the increment of insulin, higher for the gestational diabetes cohort. Indirectly, the quality of maternal glycemic control and the satisfactory perinatal outcome have proven that the treatment protocol was adequate and did not depend on the type of diabetes.